SDF7, a group of Scoparia dulcis Linn. derived flavonoid compounds,stimulates glucose uptake and regulates adipocytokines in 3T3-F442a adipocytes

Ethnopharmacology relevance

Adipocytes are major tissues involved in glucose uptake second to skeletal muscle and act as the main adipocytokines mediator that regulates glucose uptake mechanism and cellular differentiation. The objective of this study were to examine the effect of the SDF7, which is a fraction consists of four flavonoid compounds (quercetin: p-coumaric acid: luteolin: apigenin=8: 26: 1: 3) from Scoparia dulcis Linn., on stimulating the downstream components of insulin signalling and the adipocytokines expression on different cellular fractions of 3T3-F442a adipocytes.

Material and methods

Morphology and lipid accumulation of differentiated 3T3-F442a adipocytes by 100 nM insulin treated with different concentrations of SDF7 and rosiglitazone were examined followed by the evaluation of glucose uptake activity expressions of insulin signalling downstream components (IRS-1, PI3-kinase, PKB, PKC, TC10 and GLUT4) from four cellular fractions (plasma membrane, cytosol, high density microsome and low density microsome). Next, the expression level of adipocytokines (TNF-α, adiponectin and leptin) and immunoblotting of treated 3T3-F442 adipocytes was determined at 30 min and 480 min. Glucose transporter 4 (GLUT4) translocation of 3T3-F442a adipocytes membrane was also determined. Lastly, mRNA expression of adiponectin and PPAR-γ of 3T3-F442a adipocytes were induced and compared with basal concentration.

Results

It was found that SDF7 was able to induce adipocytes differentiation with great extends of morphological changes, lipid synthesis and lipid stimulation in vitro. SDF7 stimulation of glucose transport on 3T3-F442a adipocytes are found to be dose independent, time-dependent and plasma membrane GLUT4 expression-dependent. Moreover, SDF7 are observed to be able to suppress TNF-α and leptin expressions that were mediated by 3T3-F442a adipocytes, while stimulated adiponectin secretion on the cells. There was a significant expression (p<0.01) of protein kinase C and small G protein TC10 on 3T3-F442a adipocytes upon treatment with SDF7 as compared to the control. SDF7 was also found to be effective in stimulating adiponectin and PPAR-γ mRNA upregulation at 50 µg/ml.

Conclusion

SDF7 exhibited good lipogenesis, adiponectinesis and glucose uptake stimulatory properties on 3T3-F442a adipocytes.     

Effect of Tectona grandis Linn. on dexamethasone-induced insulin resistance in mice

Ethnopharmacological relevance

The bark of Tectona grandis Linn. is traditionally used in the treatment of diabetes.

Aim

The present study was undertaken to investigate the effect of ethanolic extract of bark of Tectona grandis Linn. (TG) in dexamethasone-induced insulin resistance in mice.

Materials and methods

Mice were treated with prestandardised dose of dexamethasone for 22 days and effect of TG at the doses of 50, 100 and 200 mg/kg, p.o. on plasma blood glucose level, serum triglyceride level, glucose uptake in skeletal muscle, levels of hepatic antioxidant enzymes (GSH, SOD, catalase and LPO), and body weight were observed.

Results

TG showed significant decrease in plasma glucose and serum triglyceride levels (p < 0.01) at the dose of 100 and 200 mg/kg, p.o. and also stimulated glucose uptake in skeletal muscle. The levels of antioxidant enzymes GSH, SOD, and catalase were significantly increased (p < 0.01) and there was significant decrease (p < 0.01) in level of LPO.

Conclusion

Hence it can be concluded that Tectona grandis may prove to be effective in the treatment of Type-II Diabetes mellitus owing to its ability to decrease insulin resistance.     

Fruit extracts of Momordica charantia potentiate glucose uptake and up-regulate Glut-4, PPARγ and PI3K

Ethnopharmacological relevance

Momordica charantia fruit is a widely used traditional medicinal herb as, anti-diabetic, anti-HIV, anti-ulcer, anti-inflammatory, anti-leukemic, anti-microbial, and anti-tumor.

Aims of study

The present study is undertaken to investigate the possible mode of action of fruit extracts derived from Momordica charantia (MC) and study its pharmacological effects for controlling diabetic mellitus. Effects of aqueous and chloroform extracts of Momordica charantia fruit on glucose uptake and up-regulation of glucose transporter (Glut-4), peroxisome proliferator activator receptor gamma (PPARγ) and phosphatidylinositol-3 kinase (PI3K), were investigated to show its efficacy as a hypoglycaemic agent.

Materials and methods

Dose dependent glucose uptake assay was performed on L6 myotubes using 2-deoxy-d-[1-³H] glucose. Up-regulatory effects of the extracts on the mRNA expression level of Glut-4, PPARγ and PI3K have been studied.

Results

The association of Momordica charantia with the aqueous and chloroform extracts of Momordica charantia fruit at 6 μg/ml has shown significant up-regulatory effect, respectively, by 3.6-, 2.8- and 3.8-fold on the battery of targets Glut-4, PPARγ and PI3K involved in glucose transport. The up-regulation of glucose uptake was comparable with insulin and rosiglitazone which was approximately 2-fold over the control. Moreover, the inhibitory effect of the cyclohexamide on Momordica charantia fruit extract mediated glucose uptake suggested the requirement of new protein synthesis for the enhanced glucose uptake.

Conclusion

This study demonstrated the significance of Glut-4, PPARγ and PI3K up-regulation by Momordica charantia in augmenting the glucose uptake and homeostasis.     

Sarcopoterium spinosum extract as an antidiabetic agent: In vitro and in vivo study

Ethnopharmacological relevance

Sarcopoterium spinosum (L.) sp., a common plant in the Mediterranean region, is widely used as an antidiabetic drug by Bedouin healers. However, the antidiabetic properties of Sarcopoterium spinosum had not been fully validated using scientific tools.

Aim of the study

To determine the effectiveness of Sarcopoterium spinosum extract as an antidiabetic agent in vitro and in vivo.

Materials and methods

RINm pancreatic β-cells, L6 myotubes, 3T3-L1 adipocytes and AML-12 hepatocytes were treated with an aqueous Sarcopoterium spinosum extract (0.001–10 mg/ml). The effect of the extract on specific physiological functions, including insulin secretion, pancreatic β-cell viability, GSK3β phosphorylation, lipolysis and glucose uptake was measured. In vivo studies were performed using KK-A^y mice, given the extract for several weeks. IPGTT was performed, and plasma insulin, FFA, food consumption and body weight were measured. In addition, diabetic KK-A^y mice were given a single dose of the extract, and IPGTT was performed.

Results

Sarcopoterium spinosum extract increased basal and glucose/forskolin-induced insulin secretion in RINm cells, and increased cell viability. The extract inhibited lipolysis in 3T3-L1 adipocytes, and induced glucose uptake in these cells as well as in AML-12 hepatocytes and L6 myotubes. GSK3β phosphorylation was also induced in L6 myotubes, suggesting increased glycogen synthesis. Sarcopoterium spinosum extract had a preventive effect on the progression of diabetes in KK-A^y mice. Catechin and epicatechin were detected in Sarcopoterium spinosum extract using hyphenated LC–MS/MS.

Conclusions

Sarcopoterium spinosum extract has effects that mimic those of insulin and provide the basis for antidiabetic activity of the extract.     

Astragalus polysaccharide improves insulin sensitivity in KKAy mice: Regulation of PKB/GLUT4 signaling in skeletal muscle

Ethnopharmacological relevance

Astragalus polysaccharide (APS) is an important bioactive component of Astragalus membranaceus Bunge (Leguminosae) that has been used in traditional Chinese medicine for treating diabetes.

Aim of the study

To study the mechanisms by which APS ameliorates diabetes, we examined whether treatment with APS improves insulin sensitivity in insulin-resistant mice and whether this is associated with an improvement of dysregulated protein kinase B and glucose transporter 4 expressions in skeletal muscle.

Methods

APS (700 mg kg⁻¹ day⁻¹) or vehicle was administered to 12-week-old diabetic KKAy and nondiabetic C57BL/6J mice for 8 weeks. Changes in body weight, blood glucose level, insulin resistance index, and oral glucose tolerance were routinely evaluated. The expressions of protein kinase B and glucose transporter 4 in skeletal muscle tissues were determined with Western blot.

Results

KKAy mice developed persistent hyperglycemia, impaired glucose tolerance and insulin resistance. Insulin-stimulated protein kinase B phosphorylation and glucose transporter 4 translocation were significantly decreased in KKAy compared to age-matched C57BL/6J mice. APS treatment ameliorated hyperglycemia and insulin resistance. Although the content of protein kinase B and glucose transporter 4 in KKAy skeletal muscle were not affected by APS, insulin-induced protein kinase B Ser-473 phosphorylation and glucose transporter 4 translocation in skeletal muscle were partially restored by APS treatment. In contrast, APS did not have any effect on C57BL/6J mice.

Conclusions

These results indicate that APS can regulate part of the insulin signaling in insulin-resistant skeletal muscle, and that APS could be a potential insulin sensitizer for the treatment of type 2 diabetes.     

Antihyperglycemic and insulin secretory activity of Costus pictus leaf extract in streptozotocin induced diabetic rats and in in vitro pancreatic islet culture

Aim of the study

The leaves of Costus pictus D. Don were used extensively for its antihyperglycemic activity by the people in Kerala, India. In the present study, the antihyperglycemic and insulin secretory activity of an aqueous extract of Costus pictus leaf extract was investigated in streptozotocin induced diabetic rats.

Materials and methods

Oral Glucose Tolerance Test was done to determine the effective dose of Costus pictus extract. Aqueous extract of Costus pictus leaves was given orally to the diabetic rats for 14 days. The insulin secretory action of the leaf extract was investigated using isolated pancreatic islets from rat. Liver glucose uptake activity was measured using d-[¹⁴C] glucose.

Results

The oral administration of an aqueous extract of Costus pictus at a dose of 250 mg/kg body weight significantly decreased the blood glucose with significant increase in plasma insulin level in diabetic rats at the end of 14 days treatment. The Costus pictus leaf extract significantly increased glucose induced insulin secretion at both 4 mM and 20 mM glucose concentrations which represents normal physiological and diabetic condition respectively. The decreased glucose uptake activity of the liver of diabetic rats was reverted to near normal levels after the treatment with Costus pictus leaf extract.

Conclusion

Our results suggest the glucose lowering effect of Costus pictus to be associated with the potentiation of insulin release from pancreatic islets and enhancement of peripheral utilization of glucose.     

Anti-diabetic activity of Chiliadenus iphionoides

Ethnopharmacological relevance

Chiliadenus iphionoides (Boiss. & Blanche) Brullo (Asteraceae), a small aromatic shrub found throughout Israel, is used traditionally in the treatment of diabetes mellitus. In this study, Chiliadenus iphionoides anti-diabetic activity was characterized using cellular and animal models.

Materials and methods

Pancreatic β cells, adipocytes, and skeletal myotubes were treated with an ethanolic extract of Chiliadenus iphionoides to study the extract's effects on insulin secretion and glucose uptake. The sand rat (Psammomys obesus) was used to study Chiliadenus iphionoides acute and long term effects in vivo. An oral starch tolerance test was performed as well as a 30 day feeding study.

Results

Chiliadenus iphionoides extract increased insulin secretion in β cells as well as glucose uptake in adipocytes and skeletal myotubes. The extract also displayed hypoglycemic activity in the diabetic sand rat.

Conclusions

Chiliadenus iphionoides exhibits considerable anti-diabetic activity, although the mechanism of action remains to be determined.     

Involvement of the PI3K/AKT pathway in the hypoglycemic effects of saponins from Helicteres isora

Aim of the study

Saponins from Helicteres isora have previously been shown to exert antidiabetic effects. The present study explored the underlying mechanisms in C2C12 skeletal muscle cells.

Materials and methods

C2C12 cells were incubated with saponins and sapogenin followed by Western blotting and immunofluorescence analysis.

Results

Western blotting revealed that incubation with saponins (100 μg/ml) and sapogenin (100 μg/ml) induced the phosphorylation of the phosphatidylinositol-3-kinase (PI3K) as well as of the downstream targets protein kinase B/Akt (at Ser473) and glycogen synthase kinase GSK-3α/β (at Ser21/9) in a time-dependent manner. In contrast, no phosphorylation of the AMP-sensitive kinase AMPK (at Thr172) was observed. Within 48 h saponins/sapogenin treatment further increased the protein abundance of the insulin-sensitive glucose transporter Glut4. Confocal microscopy confirmed that saponins/sapogenin treatment stimulated Akt phosphorylation and revealed that the treatment was followed by translocation of Glut4 into the cell membrane of C2C12 muscle cells.

Conclusions

Saponins and sapogenin activate the PI3K/Akt pathway thus leading to phosphorylation and inactivation of GSK-3α/β with subsequent stimulation of glycogen synthesis as well as increase of Glut4-dependent glucose transport across the cell membrane.     

Anti-diabetic and anti-cataract effects of Chromolaena odorata Linn., in streptozotocin-induced diabetic rats

Ethnopharmacological relevance

Chromolaena odorata Linn., is used in traditional Indian medicine in the treatment of diabetes and eye problems.

Aim of the study

The present study was designed to investigate the effect of the ethanol extract Chromolaena odorata leaves (ACO) in streptozotocin (STZ; 45 mg/kg, i.v) induced diabetes and cataract in rats.

Materials and methods

Different doses of ACO (200 and 400 mg/kg) was administered once daily for eight weeks to STZ-induced diabetic rats. To know the mechanism of action of title plant, AUC_glucose, AUC_insulin, Homeostatic Model Assessment (HOMA), insulin tolerance test (ITT) and glucose uptake by rat hemi-diaphragms were carried out. Further, cataract score was taken once in a week upto eight weeks and opacity index was measured. HPLC fingerprinting profiling of ACO was also carried out.

Results

Administration of ACO exhibited significant reduction in glucose, HOMA, lipid profiles and significantly improved glucose and insulin tolerance, glycogen content, glucose uptake by skeletal muscle, serum insulin and HDL-c levels. In addition, ACO also decreased oxidative stress by improving endogenous antioxidants. Further, treatment of ACO showed significantly reduced onset and extent of cataract.

Conclusion

The present data suggested that the treatment of ACO reversed the STZ-induced diabetes and cataract in rats. The observed beneficial effects may be mediated by interacting with multiple targets operating in diabetes mellitus and its complication. Taken together, this study provided the scientific evidence for the traditional use of Chromolaena odorata.     

Antihyperglycemic effect of a natural chicoric acid extract of chicory (Cichorium intybus L.): A comparative in vitro study with the effects of caffeic and ferulic acids

Ethnopharmacological relevance

In Eurasia folk medicine, roots of chicory (Cichorium intybus L.) have been reported to exert antidiabetic benefits. In vitro, a natural chicoric acid extract (NCRAE) from Cichorium intybus root has been shown to increase insulin secretion by pancreatic β-cells and glucose uptake by muscle cells.

Materials and methods

In vitro experiments were designed to compare the effects of two hydroxycinnamic acids, caffeic and ferulic acids, to those obtained with NCRAE (50 and 100 µg.mL⁻¹) on the three major tissues implicated in glycemic regulation (pancreas, muscle and liver). In vivo experiments were performed in Wistar rats submitted to a daily intraperitoneal injection of NCRAE (3, 15 or 30 mg kg⁻¹) for 4 days. On the fourth day, an intraperitoneal glucose tolerance test (IPGTT; 1 g kg⁻¹) was carried out.

Results

Our results show that the three compounds we used are able each to induce an original response. Caffeic acid mainly promotes a decrease in hepatic glycogenolysis. Ferulic acid elicits a clear increase of insulin release and a reduction of hepatic glycogenolysis. However, this compound induces an inhibition of muscle glucose uptake. NCRAE provokes an increase of insulin release and glucose uptake without any effect on hepatic glycogenolysis. We could also show that none of these compounds implicates hepatic glucose 6-phosphatase in contrast to chlorogenic acid, known as an inhibitor of glucose 6-phosphatase and which is able to decrease glucose output from hepatocytes. Our results point out that NCRAE is able to decrease blood glucose without any effect hepatic effect. Our in vivo experiments bring evidence that 4 daily IP administrations of NCRAE improve IP glucose tolerance in a dose-dependent manner and mainly via an insulin sensitizing effect.

Conclusions

We conclude that NCRAE presents an antihyperglycemic effect essentially due to a peripheral effect on muscle glucose uptake.     

Cyclocarya paliurus extract modulates adipokine expression and improves insulin sensitivity by inhibition of inflammation in mice

Ethnopharmacological relevance

Cyclocarya paliurus Batal., a Chinese native plant, is the sole species in its genus and its leaves have been widely used as a remedy for diabetes in traditional folk medicine. The study was undertaken to evaluate the effects of Cyclocarya paliurus leaves extracts (CPE) on adipokine expression and insulin sensitivity in mice.

Materials and methods

Mice were stimulated with conditioned medium (prepared from activated macrophages, Mac-CM) to induce adipose dysfunction and insulin resistance. Then mice were treated with CPE (100, 200 and 500 mg/kg, ig.) or metformin (200 mg/kg, ig.), followed by glucose and insulin intolerance, adipokine expression, phosphorylation of insulin receptor substrate (IRS-1) and glucose consumption measurement.

Results

CPE, as well as metformin effectively promoted glucose disposal in oral glucose tolerance test in normal mice. Mac-CM challenge induced glucose and insulin intolerance, but CPE reversed these alternations with increased glycogen content in muscle and liver, well demonstrating its beneficial effects on glucose homeostasis. RT-qPCR analysis showed that CPE inhibited TNF-a, IL-6, MCP-1 and resistin overexpression and effectively enhanced adiponectin expression in adipose tissue when mice were exposed to Mac-CM stimulation. Inflammation impaired insulin signaling in muscle, whereas CPE inhibited inflammation-induced serine phosphorylation of IRS-1 and effectively restored the phosphorylation of both IRS-1 at tyrosine residues and downstream Akt phosphorylation in response to insulin. Moreover, independently of insulin, CPE promoted glucose consumption in adipocytes under normal and inflammatory conditions.

Conclusion

Above-mentioned results demonstrated that CPE beneficially regulated adipokines expression and ameliorated insulin resistance through inhibition of inflammation in mice.     

Ibervillea sonorae (Cucurbitaceae) induces the glucose uptake in human adipocytes by activating a PI3K-independent pathway

Ethnopharmacological relevance

Ibervillea sonorae (S. Watson) Greene (Cucurbitaceae), a plant used for the empirical treatment of type 2 diabetes in México, exerts antidiabetic effects on animal models but its mechanism of action remains unknown. The aim of this study is to investigate the antidiabetic mechanism of an Ibervillea sonorae aqueous extract (ISE).

Materials and methods

Non-toxic ISE concentrations were assayed on the glucose uptake by insulin-sensitive and insulin-resistant murine and human cultured adipocytes, both in the absence or the presence of insulin signaling pathway inhibitors, and on murine and human adipogenesis. Chemical composition of ISE was examined by spectrophotometric and HPLC techniques.

Results

ISE stimulated the 2-NBDGlucose uptake by mature adipocytes in a concentration-dependent manner. ISE 50 µg/ml induced the 2-NBDG uptake in insulin-sensitive 3T3-F442A, 3T3-L1 and human adipocytes by 100%, 63% and 33%, compared to insulin control. Inhibitors for the insulin receptor, PI3K, AKT and GLUT4 blocked the 2-NBDG uptake in murine cells, but human adipocytes were insensitive to the PI3K inhibitor Wortmannin. ISE 50 µg/ml also stimulated the 2-NBDG uptake in insulin-resistant adipocytes by 117% (3T3-F442A), 83% (3T3-L1) and 48% (human). ISE induced 3T3-F442A adipogenesis but lacked proadipogenic effects on 3T3-L1 and human preadipocytes. Chemical analyses showed the presence of phenolics in ISE, mainly an appreciable concentration of gallic acid.

Conclusion

Ibervillea sonorae exerts its antidiabetic properties by means of hydrosoluble compounds stimulating the glucose uptake in human preadipocytes by a PI3K-independant pathway and without proadipogenic effects.     

Insulin releasing and alpha-glucosidase inhibitory activity of ethyl acetate fraction of Acorus calamus in vitro and in vivo

Ethnopharmacological relevance

The radix of Acorus calamus L. (AC) is widely used in the therapy of diabetes in traditional folk medicine of America and Indonesia, and we previously reported the insulin sensitizing activity of the ethyl acetate fraction of AC (ACE).

Aim of the study

To investigate the insulin releasing and alpha-glucosidase inhibitory activity of ACE in vitro and in vivo.

Materials and methods

Insulin releasing and alpha-glucosidase inhibitory effects of different fractions from AC were detected in vitro using HIT-T15 cell line and alpha-glucosidase enzyme. Furthermore, effects of ACE orally on serum glucose were detected in fasted and glucose/amylum challenged normal mice.

Results

AC and ACE increased insulin secretion in HIT-T15 cells as gliclazide did. As in vivo results, ACE (400 and 800 mg/kg) significantly decreased fasting serum glucose, and suppressed the increase of blood glucose levels after 2 g/kg glucose loading in normal mice. In addition, ACE as a mixed-type inhibitor inhibited alpha-glucosidase activity in vitro with an IC₅₀ of 0.41 μg/ml, and 100 mg/kg of it clearly reduced the increase of blood glucose levels after 5 g/kg amylum loading in normal mice.

Conclusions

Apart from its insulin sensitizing effect, ACE may have hypoglycemic effects via mechanisms of insulin releasing and alpha-glucosidase inhibition, and thus improves postprandial hyperglycemia and cardiovascular complications.     

In vitro anti-breast cancer activity of ethanolic extract of Wrightia tomentosa: role of pro-apoptotic effects of oleanolic acid and urosolic acid

Ethnopharmacological relevance

Pterocarpus marsupium Roxb. (PM) is an Ayurvedic traditional medicine well known for its antidiabetic potential.

Aim

To fractionate the antidiabetic constituent(s) of the aqueous of extract of PM hardwood (PME).

Materials and methods

Bio-assay methods including, insulin secretion from mouse pancreas and glucose uptake by mouse skeletal muscle, were used to determine and fractionate the antidiabetic activity of PME. Results obtained from the in vitro experiments were then verified by examining the effect of PME on glucose clearance in normoglycemic, non-diabetic sheep in vivo.

Results

Exposure of mouse pancreatic and muscle tissues to PME stimulated the insulin secretion and glucose uptake, respectively, in a concentration-dependent manner. PME-mediated muscle glucose uptake was not potentiated in the presence of insulin indicating that PME acts via pathways which are utilized by insulin. Bio-assay-guided fractionation of PME yielded a high molecular weight fraction which had potent antidiabetic properties in vitro, and in in vivo.

Conclusions

Our findings, we believe for the first time, provide novel insights for the antidiabetic constituents of PM and demonstrate that a high molecular weight constituent(s) of PM has potent insulinotrophic and insulin-like properties.     

Acute effects of Fraxinus excelsior L. seed extract on postprandial glycemia and insulin secretion on healthy volunteers

Aim of the study

Fraxinus excelsior L. (Family: Oleaceae) seeds are consumed as a food, condiment, and folk medicine. The seeds are traditionally used as a potent hypoglycemic agent, but no clinical evidence exists in as to this regard. We assessed the clinical efficacy and safety of the seed extract (FraxiPure™, Naturex), containing 6.8% of nuzhenide and 5.8% of GI3 (w/w), on plasma glucose and insulin levels against glucose (50 g) induced postprandial glycemia.

Materials and methods

Preselected dose (1.0 g) was used in a double blind, randomized, crossover, placebo (wheat bran) controlled study on 16 healthy volunteers. Each treatment was given immediately after a fasting blood glucose sample (0 min). Postprandial plasma glucose levels were estimated at 0, 15, 30, 45, 60, 90 and 120 min; and postprandial plasma insulin at 0, 30, 60, 90 and 120 min.

Results

The extract lowered the incremental postprandial plasma glucose concentration as compared to placebo at 45 min (P = 0.06) and 120 min (P = 0.07). It statistically (P = 0.02) reduced the glycemic area under the blood glucose curve. The seed, also, induced a significant (P = 0.002) secretion of insulin at 90 min after glucose administration. However, the insulinemic area under the blood insulin curve was not different than the placebo. No adverse events were reported.

Conclusions

Our findings confirm the hypoglycemic action of Fraxinus excelsior L. seed extract. These promising results, thus, encourage conducting long-term clinical studies to further evaluate the efficacy and safety of Fraxinus excelsior L. seed extract in healthy and diabetic volunteers and also to explore the possible mechanism(s) of action.     

Anti-diabetic effects of Centratherum anthelminticum seeds methanolic fraction on pancreatic cells, β-TC6 and its alleviating role in type 2 diabetic rats

Ethnopharmacological relevance

Seeds of Centratherum anthelminticum (Asteraceae) have been popularly used in Ayurvedic medicine to treat diabetes and skin disorders. Folk medicine from Rayalaseema (Andhra Pradesh, India) reported wide spread usage in diabetes.

Aim of the study

To investigate the hypoglycemic properties and mechanism of the methanolic fraction of C. anthelminticum seeds (CAMFs) on mouse β-TC6 pancreatic cell line and streptozotocin (STZ)-induced diabetic rat models.

Materials and Methods

We investigated the crude methanolic fraction of C. anthelminticum seeds (CAMFs) on β-TC6 cell line and confirmed its effects on type 1 and type 2 diabetic rats to understand its mechanism in managing diabetes mellitus. CAMFs were initially tested on β-TC6 cells for cytotoxicity, 2-NBDG glucose uptake, insulin secretion and glucose transporter (GLUT-1, 2 and 4) protein expression. Furthermore, streptozotocin (STZ)-induced type 1 diabetic and STZ-nicotinamide-induced type 2 diabetic rats were intraperitoneally (i.p) injected or administered orally with CAMFs daily for 28 days. The effect of CAMFs on blood glucose and insulin levels was subsequently evaluated.

Results

In cell line studies, CAMFs showed non-cytotoxic effect on β-TC6 cell proliferation compared to untreated control cells at 50 μg/ml. CAMFs increased glucose uptake and insulin secretion dose-dependently by up-regulating GLUT-2 and GLUT-4 expression in these cells. Further in vivo studies on streptozotocin induced diabetic rat models revealed that CAMFs significantly reduced hyperglycemia by augmenting insulin secretion in type 2 diabetic rats. However, CAMFs displayed less significant effects on type 1 diabetic rats.

Conclusions

CAMFs demonstrated anti-diabetic potential on β-TC6 cells and type 2 diabetic rat model, plausibly through enhancing glucose uptake and insulin secretion.     

Cinchonain Ib isolated from Eriobotrya japonica induces insulin secretion in vitro and in vivo

Aims of the study

Eriobotrya japonica leaves had been used traditionally for the treatment of diabetes mellitus by immersing the dried leaves in a hot water drink. Few studies have shown the hypoglycemic effect of Eriobotrya japonica using crude alcoholic extract and isolated methanolic compounds. These studies proposed that the mechanism of action could be by stimulating the β-islets of Langerhans to secrete insulin, however with no scientific evidence.

Methods

Eriobotrya japonica water extract (EJWE) and the compounds derived from it: cinchonain Ib, procyanidin B-2, chlorogenic acid and epicatechin, were tested for their effects on insulin secretion from INS-1 cells and following oral administration in rats.

Results

The present study showed that EJWE increased significantly (p < 0.05) insulin secretion from INS-1 cells in dose-dependent manner. Oral administration of EJWE at 230 mg/kg to rats, however, decreased plasma insulin level for as long as 240 min post-administration and caused a transient drop of blood glucose at 15 and 30 min post-administration. On the other hand, cinchonain Ib enhanced significantly (p < 0.05) insulin secretion from INS-1 cells, whereas epicatechin inhibited significantly (p < 0.05) insulin secretion from INS-1 cells. In addition, cinchonain Ib enhanced significantly (150%: p < 0.05) plasma insulin level in rats for as long as 240 min after 108 mg/kg oral administration but did not induce any change in blood glucose level.

Conclusion

These data indicate that cinchonain Ib has an insulinotropic effect and suggest the possible use of cinchonain Ib for managing type 2 diabetes.     

Ameliorative effect of Eucommia ulmoides Oliv. leaves extract (ELE) on insulin resistance and abnormal perivascular innervation in fructose-drinking rats

Aim of the study

Eucommia ulmoides Oliv. leaf is a traditional Chinese medicine that exhibits an anti-diabetic action. This study was designed to investigate whether long-term administration of Eucommia ulmoides Oliv. leaves extract (ELE) ameliorates pre-diabetic state of insulin resistance and abnormal perivascular innervation in the hyperinsulinemic state.

Materials and methods

ELE at doses of 500 and 1000 mg/kg was administered orally once daily for 4 weeks in fructose-drinking rats (FDRs). Plasma levels of insulin, blood glucose levels, and perivascular innervation were assessed using biochemical and immunohistochemical methods.

Results

FDR showed significant increase in plasma levels of insulin, an index for insulin resistance (Homeostasis Model Assessment ratio—HOMA-IR) and systolic blood pressure (SBP), but not blood glucose levels, as compared with control rats. Immunohistochemical study showed significantly greater density of tyrosine hydroxylase (TH)-like immunoreactivity (LI)-containing nerves and significantly lower density of calcitonin gene-related peptide (CGRP)-LI-containing nerves in mesenteric arteries of FDR than those in control. A 4-week treatment with ELE (500 and 1000 mg/kg, p.o.) significantly decreased plasma levels of insulin and HOMA-IR without affecting blood glucose levels and significantly lowered SBP in FDR. ELE treatment in FDR resulted in significant increase in CGRP-LI never fiber density and significant decrease in TH-LI never fiber density in mesenteric arteries of FDR.

Conclusions

These results suggest that long-term ELE treatment effectively prevents insulin resistance development and ameliorates abnormal perivascular innervation in FDR.     

Neferine enhances insulin sensitivity in insulin resistant rats

Ethnopharmacological relevance

Neferine was isolated from green seed embryo of Nelumbo nucifera Gaertn which has been used as an anti-obesity agent in traditional Chinese herbal medicine.

Aim of the study

This study was conducted to investigate the effects of neferine on enhancing insulin sensitivity in insulin resistant rats compared with rosiglitazone and to potentially reveal its role in mediating the anti-obesity properties of Nelumbo nucifera Gaertn.

Materials and methods

Fasting blood glucose (FBG), fasting blood insulin (FINS), triglycerides (TG) and tumor necrosis factor-α (TNF-α) were measured, and the oral glucose tolerance test for 2-h plasma glucose level (2-h PG) was carried out. The glucose infusion rate (GIR) was used to measure the insulin sensitivity by hyperinsulinemic euglycemic clamp technique.

Results

The levels of FBG, FINS, TG, TNF-α and 2-h PG all decreased significantly in the rosiglitazone and neferine groups compared with the insulin resistance (IR) model group. Neferine diminished the 2-h PG more than did rosiglitazone treatment. Compared to the IR model group, the treatments of neferine and rosiglitazone remarkably increased GIRs but no difference between these two treatments themselves was evident.

Conclusions

These data demonstrate that neferine has effects similar to rosiglitazone in decreasing fasting blood glucose, insulin, TG, TNF-α and enhancing insulin sensitivity in insulin resistant rats.